Publications

IMPORTANCE: Drug shortages are a chronic and worsening issue that compromises patient safety. Despite the destabilizing impact of the COVID-19 pandemic on pharmaceutical production, it remains unclear whether issues affecting the drug supply chain were more likely to result in meaningful shortages during the pandemic.

OBJECTIVE: To estimate the proportion of supply chain issue reports associated with drug shortages overall and with the COVID-19 pandemic.

DESIGN, SETTING, AND PARTICIPANTS: This longitudinal cross-sectional study used data from the IQVIA Multinational Integrated Data Analysis database, comprising more than 85% of drug purchases by US pharmacies from wholesalers and manufacturers, from 2017 to 2021. Data were analyzed from January to May 2023.

EXPOSURE: Presence of a supply chain issue report to the US Food and Drug Administration or the American Society of Health-Systems Pharmacists (ASHP).

MAIN OUTCOMES AND MEASURES: The main outcome was drug shortage, defined as at least 33% decrease in units purchased within 6 months of a supply chain issue report. Random-effects logistic regression models compared the marginal odds of shortages for drugs with vs without reports. Interaction terms assessed heterogeneity prior to vs during the COVID-19 pandemic and by drug characteristics (formulation, age, essential medicine status, clinician- vs self-administered, sales volume, and number of manufacturers).

RESULTS: A total of 571 drugs exposed to 731 supply chain issue reports were matched to 7296 comparison medications with no reports. After adjusting for drug characteristics, 13.7% (95% CI, 10.4%-17.8%) of supply chain issue reports were associated with subsequent drug shortages vs 4.1% (95% CI, 3.6%-4.8%) of comparators (marginal odds ratio [mOR], 3.7 [95% CI, 2.6-5.1]). Shortages increased among both drugs with and without reports in February to April 2020 (34.2% of drugs with supply chain issue reports and 9.5% of comparison drugs; mOR, 4.9 [95% CI, 2.1-11.6]), and then decreased after May 2020 (9.8% of drugs with reports and 3.6% of comparison drugs; mOR, 2.9 [95% CI, 1.6-5.3]). Significant associations were identified by formulation (parenteral mOR, 1.9 [95% CI, 1.1-3.2] vs oral mOR, 5.4 [95% CI, 3.3-8.8]; P for interaction = .008), WHO essential medicine status (essential mOR, 2.2 [95% CI, 1.3-5.2] vs nonessential mOR, 4.6 [95% CI, 3.2-6.7]; P = .02), and for brand-name vs generic status (brand-name mOR, 8.1 [95% CI, 4.0-16.0] vs generic mOR, 2.4 [95% CI, 1.7-3.6]; P = .002).

CONCLUSIONS AND RELEVANCE: In this national cross-sectional study, supply chain issues associated with drug shortages increased at the beginning of the COVID-19 pandemic. Ongoing policy work is needed to protect US drug supplies from future shocks and to prioritize clinically valuable drugs at greatest shortage risk.

BACKGROUND: Valsartan is commonly used for cardiac conditions. In 2018, the Food and Drug Administration recalled generic valsartan due to the detection of impurities. Our objective was to determine if heart failure patients receiving valsartan at the recall date had a greater likelihood of unfavorable outcomes than patients using comparable antihypertensives.

METHODS: We conducted a cohort study of Optum's de-identified Clinformatics® Datamart (July 2017-January 2019). Heart failure patients with commercial or Medicare Advantage insurance who received valsartan were compared to persons who received non-recalled angiotensin receptor blockers (ARBs) and angiotensin converting enzyme-inhibitors (ACE-Is) for 1 year prior and including the recall date. Outcomes included a composite for all-cause hospitalization, emergency department (ED), and urgent care (UC) use and a measure of cardiac events which included hospitalizations for acute myocardial infarction and hospitalizations/ED/UC visits for stroke/transient ischemic attack, heart failure or hypertension at 6-months post-recall. Cox proportional hazard models with propensity score weighting compared the risk of outcomes between groups.

RESULTS: Of the 87 130 adherent patients, 15% were valsartan users and 85% were users of non-recalled ARBs/ACE-Is. Valsartan use was not associated with an increased risk of all-cause hospitalization/ED/UC use six-months post-recall (HR 1.00; 95% CI 0.96-1.03), compared with individuals taking non-recalled ARBs/ACE-Is. Similarly, cardiac events 6-months post-recall did not differ between individuals on valsartan and non-recalled ARBs/ACE-Is (HR 1.04; 95% CI 0.97-1.12).

CONCLUSIONS: The valsartan recall did not affect short-term outcomes of heart failure patients. However, the recall potentially disrupted the medication regimens of patients, possibly straining the healthcare system.

OBJECTIVES: Not much is known about safety checklists use in dentistry. We aim to examine, assess, and provide a comprehensive understanding of the current knowledge concerning the use of checklists to improve patient safety in dentistry.

METHODS: We conducted a comprehensive literature search using Medline and Embase for studies that use or describe the development of dental patient safety checklists. All study designs were included for citations published through December 2023.

RESULTS: Following abstract and full-text screening, 27 studies remained for data extraction and analysis. Oral surgery emerged as the main dental specialty where the utilization and evaluation of checklists were primarily concentrated (n = 15). The majority of the included studies described either checklist development, their implementation, or both (n = 18). Only 6 studies assessed the effectiveness of checklists in improving patient safety outcomes. Of the effectiveness studies, five found a decrease in incidents and dental adverse events, along with an improvement in patient care and safety, associated with the use of checklists.

CONCLUSIONS: This scoping review highlights the limited current knowledge regarding checklist use and effectiveness in reducing adverse events across dental practices; it demonstrates the need on how to best guide the profession towards implementing this important evidence-based patient safety tool.

CLINICAL RELEVANCE: Checklists are effective tools to improve patient safety and have become integral to medical practice. Dentistry can also benefit from these tools to improve patient safety.

OBJECTIVE: The US National Action Plan for Combating Antibiotic-Resistant Bacteria established a goal to decrease unnecessary outpatient antibiotic use by 50%. However, data to inform this goal have been limited to medical settings and have not included dental prescribing. Thus, we sought to identify the proportion of antibiotics prescribed inappropriately by dentists to inform outpatient stewardship efforts.

METHODS: Cross-sectional analysis of 2019 Veterans' Affairs (VA) national electronic health record data. Antibiotics prescribed by dentists were evaluated for appropriateness based on 2 definitions: one derived from current guidelines (consensus-based recommendations) and the other based on relevant clinical literature (nonconsensus). A clustered binomial logistic regression model determined factors associated with discordant prescribing.

RESULTS: In total, 92,224 antibiotic prescriptions (63% amoxicillin; mean supply, 8.0 days) were associated with 88,539 dental visits. Prophylaxis for complications in medically compromised patients was associated with the most (30.9%) antibiotic prescriptions, followed by prevention of postsurgical complications (20.1%) and infective endocarditis (18.0%). At the visit level, 15,476 (17.5%) met the consensus-based definition for appropriate antibiotic usage and 56,946 (64.3%) met the nonconsensus definition.

CONCLUSIONS: More than half of antibiotics prescribed by dentists do not have guidelines supporting their use. Regardless of definition applied, antibiotics prescribed by dentists were commonly unnecessary. Improving prescribing by dentists is critical to reach the national goal to decrease unnecessary antibiotic use.

INTRODUCTION: Dry socket and infection are complications of tooth extractions. The objective was to determine risk factors for post-extraction complications in patients without antibiotic prophylaxis stratified by early- and late-complications and complication type (oral infection and dry socket).

METHODS: Retrospective, case (with complications)-control (without complications) study of patients (n = 708) who had ≥1 extraction performed at any Veterans Health Administration facility between 2015-2019 and were not prescribed an antibiotic 30 days pre-extraction.

RESULTS: Early complication cases (n = 109) were more likely to be female [odds ratio (OR) = 2.06; 95% confidence interval (CI):1.05-4.01], younger (OR = 0.29; 95% CI:0.09-0.94 patients ≥ 80 years old, reference:18-44 years), Native American/Alaska Native (OR = 21.11; 95% CI:2.33-191.41) and have fewer teeth extracted (OR = 0.53 3+ teeth extracted; 95% CI:0.31-0.88, reference:1 tooth extracted). Late complication cases (n = 67) were more likely to have a bipolar diagnosis (OR = 2.98; 95% CI:1.04-8.57), history of implant placement (OR = 8.27; 95% CI:1.63-41.82), and history of past smoking (OR = 2.23; 95% CI:1.28-3.88).

CONCLUSION: Predictors for post-extraction complications among patients who did not receive antibiotic prophylaxis were similar to prior work in cohorts who received prophylaxis. Unique factors identified in a medically complex population included being younger, Native American/Alaska Native, having mental health conditions, history of a dental implant, and fewer teeth extracted.

OBJECTIVES: While factors contributing to dental antibiotic overprescribing have previously been described, previous work has lacked any theoretical behavior change framework that could guide future intervention development. The purpose of this study was to use an evidence-based conceptual model to identify barriers and facilitators of appropriate antibiotic prescribing by dentists as a guide for future interventions aimed at modifying antibiotic prescribing.

METHODS: Semi-structured interviews were conducted with dentists from the National Dental Practice Based Research Network (PBRN) exploring patient and practice factors perceived to impact antibiotic prescribing. Audio-recorded telephone interviews were transcribed and independently coded by three researchers. Themes were organized around the COM-B model to inform prospective interventions.

RESULTS: 73 of 104 dentists (70.1%) were interviewed. Most were general dentists (86.3%), male (65.7%), and white (69.9%). Coding identified three broad targets to support appropriate dental antibiotic prescribing among dentists: (1) increasing visibility and accessibility of guidelines, (2) providing additional guidance on antibiotic prescribing in dental scenarios without clear guidelines, and (3) education and communication skills-building focused on discussing appropriate antibiotic use with patients and physicians.

CONCLUSIONS: The findings from our study are consistent with other studies focusing on antibiotic prescribing behavior in dentists. Understanding facilitators and barriers to dental antibiotic prescribing is necessary to inform targeted interventions to improve appropriate antibiotic prescribing. Future interventions should focus on implementing multimodal strategies to provide the necessary support for dentists to judiciously prescribe antibiotics.

BACKGROUND: Ceftazidime/avibactam is one of the preferred treatment options for carbapenem-resistant Enterobacterales (CRE). However, the benefit of combining ceftazidime/avibactam with another antibiotic remains unclear.

OBJECTIVES: To identify variables associated with treatment failure during the use of ceftazidime/avibactam for CRE infections and assess the effect of combining an aminoglycoside with ceftazidime/avibactam.

METHODS: This was a retrospective cohort study of patients with a positive CRE culture treated with ceftazidime/avibactam between 2015 and 2021 in 134 Veterans Affairs (VA) facilities. The primary outcome was 30-day mortality and the secondary outcome was in-hospital mortality. A subanalysis in patients who received an aminoglycoside was also performed.

RESULTS: A total of 303 patients were included. The overall 30-day and in-hospital mortality rates were 12.5% and 24.1%, respectively. Age (aOR 1.052, 95% CI 1.013-1.093), presence in the ICU (aOR 2.704, 95% CI 1.071-6.830), and receipt of an aminoglycoside prior to initiation of ceftazidime/avibactam (aOR 4.512, 95% CI 1.797-11.327) were independently associated with 30-day mortality. In the subgroup of patients that received an aminoglycoside (n = 77), their use in combination with ceftazidime/avibactam had a 30-day mortality aOR of 0.321 (95% CI, 0.089-1.155).

CONCLUSION: In veterans treated with ceftazidime/avibactam for CRE infections, increased age, receipt of an empiric aminoglycoside, and presence in the ICU at the time of index culture were associated with higher 30-day mortality. Among patients who received an aminoglycoside, their use in combination with ceftazidime/avibactam trended toward protectiveness of 30-day mortality, suggesting a potential role for this combination to treat CRE infections in patients who are more severely ill.

Inappropriate urinary tract infection diagnosis in patients with neurogenic bladder may result from ambiguous symptoms experienced by these patients and contributes to antibiotic overuse. Characterization of patient-reported signs and symptoms may help providers more appropriately diagnose urinary tract infections. A previous study collected signs and symptoms recorded in electronic medical records of patients with neurogenic bladder due to spinal cord injury/disorder, multiple sclerosis, and Parkinson's disease with at least one urinary tract infection diagnosis between 2017-2018 at four medical centers. In this study, 23 veterans from this cohort with urinary tract infection diagnoses in the previous year participated in focus groups conducted May 2021-May 2022. Transcripts were coded using mixed deductive and inductive coding. Qualitative data were compared to electronic medical records data to give a comprehensive picture of signs and symptoms. Both providers and patients attributed nonspecific symptoms like urine changes to urinary tract infection, but there was discordance between patients and providers in the identification of other signs and symptoms. Several patients described providers disregarding symptoms other than fever or chills. Optimizing urinary tract infection care for patients with neurogenic bladder could involve improving patient-provider communication about urinary tract infection signs and symptoms and emphasizing thorough elicitation and evaluation of all signs and symptoms.

BACKGROUND: Per capita spending on drugs in the United States is double that of Canada. One commonly debated point when comparing the 2 countries is whether this additional spending allows residents of the United States access to valuable therapies not available in Canada.

OBJECTIVE: To characterize the therapeutic value of prescription drugs used in the United States that are not marketed in Canada.

METHODS: This cross-sectional study used IQVIA Multinational Integrated Data Analysis System data to identify drugs purchased in the United States but not in Canada from 2017 to 2021. Drug listing and regulatory review statuses were obtained. We categorized the drugs into 8 mutually exclusive groups: listing status in Canada ("cancelled post-market" or "dormant; approved but not marketed; cancelled pre-market"), other alternatives available ("formulation unavailable," "existing drug class," or "therapeutically similar"), "pre-approval," "atypical access available," or "unavailable without alternatives marketed" in Canada. Therapeutic value assessments of drugs in the last category were obtained from 3 international organizations.

RESULTS: 2,084 products were purchased in the United States but not in Canada from 2017 to 2021; 1,685 were excluded because they were not prescription drugs, were combinations in which each active pharmaceutical ingredient was already available in the United States as a separate drug, had been discontinued in the United States by August 30, 2023, or were marketed in Canada by August 30, 2023. After exclusions, there were 399 drugs; 120 (30%) were "cancelled post-market," 38 (10%) were "dormant; approved but not marketed; cancelled pre-market," 49 (12%) were "formulation unavailable," 130 (33%) were "existing drug class," 35 (9%) were "therapeutically similar," 3 (1%) were "preapproval," 15 (4%) were "atypical access available," and 9 (2%) were "unavailable" in Canada. 6 of the 9 drugs had been evaluated by 1 or more independent organizations, and all 6 were rated as offering minor to no additional therapeutic value compared with existing drugs.

CONCLUSIONS: There was similar access to important prescription drug therapies in the United States and Canada. Overall, the additional spending in the United States may not have necessarily translated into access to important therapeutic innovations.